AB0024 GENE EXPRESSION OF ABCG2, ALPK1, SLC22A12 AND IL-1Β IN PERIPHERAL BLOOD LEUKOCYTES OF GOUT PATIENTS WERE CORRELATED WITH THEIR COMORBIDITIES AND HYPERURICEMIA
Authors: A. López Macay, K. Martinez Flores, J. Fernández-Torres, Y. Zamudio, F. Sanchez Muñoz, D. Clavijo-Cornejo
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Genes ABCG2, SLC22A12 (URAT1), and ALPK1 have been strongly associated with dysfunction of urate metabolism in patients with gout [1], but it is unknown how these transporters are expressed in patients with acute or chronic gout. Studies in murine and in vitro models have suggested that the enzyme ALPK1 kinase and the urate transporters ABCG2 and URAT1 may be involved in urate dysregulation and inflammation due to the presence of monosodium urate crystals [2-3]. It is important to know if the patient with acute or chronic gout can differentially express these genes in different tissues. Likewise, it is necessary to know if the patient's comorbidities may be associated with the expression of these transporters or pro-inflammatory molecules such as ALPK1 or IL-1β. <h3>Objectives</h3> To analyze the expression of urate transporters ABCG2, SLC22A12 and inflammation molecules ALPK1 and IL-1β in peripheral blood leukocytes from gout patients and to compare them with their metabolic profile and with the gene expression of people without gout and without hyperuricemia. <h3>Methods</h3> A total of 36 chronic and acute patients and 52 controls were recruited, ABCG2, SLC22A12, IL-1β and ALPK1 gene expression was evaluated by quantitative real-time PCR. Correlations of gene expression with clinical and laboratory parameters of patients were also analyzed. <h3>Results</h3> IL-1β was significantly increased in Peripheric blood monocytes cells (PBMCs) of patients when compared with their polymorphnuclear leukocytes (PMNLs) (p&lt;0.05). A significant increase in ABCG2 were found in PMNLs from patients compared to controls (p&lt;0.05) and in hyperuricemic patients compared to normouricemic patients (p&lt;0.05) (see Figure 1). Correlations of gene expression in patients were related to levels of serum uric acid (sUA), serum creatinine, CRP, triglycerides, BMI, kidney disease, hypertension, and metabolic syndrome. <h3>Conclusion</h3> Our data suggest that the leukocyte cells of the patients respond to the presence hyperuricemia and comorbidities expressing ABCG2 gene differentially compared to normouricemic and non disease state. Hyperuricemia, dyslipidemias and obesity should stimulate the differential gene expression of peripheral blood leukocytes (neutrophils and monocytes) even in an asymptomatic stat.e. <h3>References</h3> [1]Tu HP, Min-Shan Ko A, Lee SS, Lee CP, Kuo TM, Huang CM, et al. Variants of ALPK1 with ABCG2, SLC2A9, and SLC22A12 increased the positive predictive value for gout. J Hum Genet. 2018;63(1):63-70. [2]Lee CP, Chiang SL, Ko AM, Liu YF, Ma C, Lu CY, et al. ALPK1 phosphorylates myosin IIA modulating TNF-alpha trafficking in gout flares. Scientific reports. 2016;6:25740. [3]Novikov A, Fu Y, Huang W, Freeman B, Patel R, van Ginkel C, et al. SGLT2 inhibition and renal urate excretion: the role of luminal glucose, GLUT9 and URAT1. American journal of physiology Renal physiology. 2018;1(316): F173-185 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.